ArticleCell2024
CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multi-omics and high-spatial-resolution omics: deciphering complexity in neurological disorders.GigaScience · 2025Pooled it
- Exploratory bidirectional Mendelian randomisation analysis of cerebrospinal fluid metabolites associated with cerebral palsy and epilepsy.BMJ paediatrics open · 2026Article
- Deciphering the rules of regulated cell death subroutines by in silico methods.Journal of advanced research · 2026Review
- Epigenetic aging in Alzheimer's disease: Relation to proteome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Proteomic comparison of human neural cell-derived extracellular vesicles and parental cells from Alzheimer's disease and cognitively normal individuals.Science China. Life sciences · 2026Article
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- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- A plasma protein signature for cerebral amyloid angiopathy.Acta neuropathologica · 2026Article
- hUCMSC mitochondrial EVs confer neuroprotection after ischemia by Tom1l2-mediated mitochondrial fusion and Crls1-cardiolipin axis reprogramming.Redox biology · 2026Article
- GPND-AI NULISA: A 15-Protein AI classifier for diagnosis and co-pathology profiling across neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026Article
- Reproducibility-driven discovery and systematic benchmarking reveal a robust cerebrospinal fluid proteomic signature in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Aging-related matrix metallopeptidase 10 and osteopontin levels are associated with pathology, cognitive decline, and age at onset in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2026Article
- APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform.Journal of lipid research · 2026Article
- Hypothalamic malate dehydrogenase 2 modulates systemic glucose metabolism through oxytocin-mediated thermogenesis.Cell reports. Medicine · 2026Article
- Integrated Structural and Glycoproteomic Profiling Reveals Protein Conformational Remodeling and Biomarkers Across Alzheimer's Disease Progression.ACS central science · 2026Article
- CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex-specific alteration of multiple proteins involved in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
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Authors and funding
42 authors.
Yuanyuan ShenDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Jigyasha TimsinaDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Gyujin HeoDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Aleksandra BericDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Muhammad AliDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Ciyang WangDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Chengran YangDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Yueyao WangDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Daniel WesternDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Menghan LiuDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Priyanka GorijalaDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
John BuddeDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Anh DoDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA.
Haiyan LiuDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Brian GordonDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jorge J Llibre-GuerraDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Nelly Joseph-MathurinMallinckrodt Institute of Radiology, Washington University St Louis, St Louis, MO 63110, USA.
Richard J PerrinDepartment of Pathology and Immunology, Washington University St. Louis, St. Louis, MO 63110, USA.
Dario MaschiDepartment of Cell Biology and Physiology, Washington University St. Louis, St. Louis, MO 63110, USA.
Tony Wyss-CorayWu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA; Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Pau PastorUnit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona 08916, Spain.
Alan E RentonRonald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ezequiel I SuraceLaboratory of Neurodegenerative Diseases, Institute of Neurosciences (INEU-Fleni-CONICET), Buenos Aires, Argentina.
Erik C B JohnsonGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA 30307, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30307, USA.
Allan I LeveyDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30307, USA.
Ignacio AlvarezDepartment of Neurology, University Hospital Mútua de Terrassa and Fundació Docència i Recerca Mútua de Terrassa, Terrassa 08221, Barcelona, Spain.
Johannes LevinDepartment of Neurology, LMU University Hospital, LMU Munich, Munich 80336, Germany; German Center for Neurodegenerative Diseases, site Munich, Munich 80336, Germany.
John M RingmanAlzheimer's Disease Research Center, Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA 90033, USA.
Ricardo Francisco AllegriDepartment of Cognitive Neurology, Neuropsychology and Neuropsychiatry, FLENI, Buenos Aires, Argentina.
Nicholas SeyfriedDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30307, USA.
Gregg S DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, FL 32224, USA.
Qisi WuDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
M Victoria FernándezFundacio ACE Institut de Neurosciencies Aplicades, Barcelona 08029, Spain.
Rawan TarawnehThe University of New Mexico, Albuquerque, NM 87131, USA.
Eric McDadeDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
John C MorrisDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Alison GoateRonald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Dominantly Inherited Alzheimer Network
Laura IbanezDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Yun Ju SungDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: cruchagac@wustl.edu.
Funding
DIAN-TU Primary Prevention Trial NfL Characterization Admin SuppU01AG059798 · NIA · WASHINGTON UNIVERSITY · PI MCDADE, ERIC MARTIN · 2018 to 2025
$97.9MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI CHENGJIE XIONG · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MResearch Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0MIdentification and Characterization of Cell-Specific Transposable Elements Implicated on Alzheimer Disease and Healthy AgingR01AG078964 · NIA · WASHINGTON UNIVERSITY · PI Carlos Cruchaga, Bess Frost · 2022 to 2026
$9.0MUSING QUANTITATIVE TRAITS TO IDENTIFY NOVEL GENES FOR ALZHEIMERS DISEASE AND OTHER COMPLEX TRAITSRF1AG053303 · NIA · WASHINGTON UNIVERSITY · PI CLIMER, SHARLEE, CRUCHAGA, CARLOS · 2016 to 2020
$4.0MIdentifying Rare Variants that Increase Risk for Alzheimer's DiseaseRF1AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2019 to 2019
$3.6MGENETIC MODIFIERS OF CEREBROSPINAL FLUID TREM2 IN ALZHEIMER'S DISEASERF1AG058501 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, PICCIO, LAURA · 2018 to 2018
$3.5MThe Familial Alzheimer Sequencing (FASe) ProjectU01AG058922 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2018 to 2022
$3.5MSex-specific Molecular Profiling to Understand Pathology and Identify Causal Genes and Drug Targets for Alzheimer's DiseaseRF1AG074007 · NIA · WASHINGTON UNIVERSITY · PI SUNG, YUNJU · 2021 to 2021
$2.7MIDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7MMultimodal Characterization of the Role of Circular RNAs in Alzheimer's DiseaseRF1AG071706 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2022 to 2022
$2.3MNIA NIH HHS K01 AG080123NIA NIH HHS P01 AG003991NIA NIH HHS P30 AG066514NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG059798NIA NIH HHS R01 AG078964NIA NIH HHS RF1 AG044546NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG071706NIA NIH HHS RF1 AG074007NIA NIH HHS RF1 AG083744NIA NIH HHS U01 AG058922NIA NIH HHS U01 AG059798NIA NIH HHS U19 AG032438
Abstract
In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups. We validated our findings with independent ADAD as well as sporadic AD datasets and employed machine learning to develop and validate predictive models. Our study identified 137 proteins with distinct trajectories between MCs and NCs, including eight that changed before traditional AD biomarkers. These proteins are grouped into three stages: early stage (stress response, glutamate metabolism, neuron mitochondrial damage), middle stage (neuronal death, apoptosis), and late presymptomatic stage (microglial changes, cell communication). The predictive model revealed a six-protein subset that more effectively differentiated MCs from NCs, compared with conventional biomarkers.
Indexed as
Alzheimer DiseaseBiomarkersProteomicsAdultAgedFemaleHumansMachine LearningMaleMiddle AgedMutationBiomarkersautosomal dominant Alzheimer’s diseasemicrogliamitochondrial damageneurodegenerationneuronal deathproteomicspseudotrajectory analysisSomascan
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